Research Traumatic Brain Injury Model Research Articles

Article 3 (see Poster 14): Amantadine Hydrochloride for Treatment of Symptoms of the Posttraumatic Confusional State: A Randomized, Double-Blind, Placebo-Controlled Trial

Objective: To test the hypothesis that amantadine hydrochloride (AH), an NMDA antagonist and indirect dopamine receptor agonist, hastens resolution of symptoms of the posttraumatic confusional state (PTCS) observed during early recovery from severe nonpenetrating traumatic brain injury (TBI). Design: Randomized, double-blind, placebo-controlled, parallel group trial. Setting: Inpatient brain injury unit of free-standing rehabilitation hospital affiliated with the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems of Care.

Poster 14 (see Article 3): Amantadine Hydrochloride for Treatment of Symptoms of the Posttraumatic Confusional State: A Randomized, Double-Blind, Placebo-Controlled Trial

Objective: To test the hypothesis that amantadine hydrochloride (AH), a NMDA antagonist and indirect dopamine receptor agonist, hastens resolution of symptoms of the posttraumatic confusional state (PTCS) observed during early recovery from severe nonpenetrating traumatic brain injury (TBI). Design: Randomized, double-blind, placebo-controlled, parallel group trial. Setting: Inpatient brain injury unit of free-standing rehabilitation hospital affiliated with the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems of Care. Participants: Consented neurorehabilitation admissions with posttraumatic confusion after initial nonpenetrating TBI ≤ 90 days earlier (n=79), randomly assigned to the AH (n=39) or placebo (n=40) groups. Group assignment was adjusted for baseline confusion severity at time of randomization. Intervention: AH 100mg twice daily or identical placebo for 14 days, or until confusion symptom resolution (if ≤14d) as measured by the Confusion Assessment Protocol (CAP). Main Outcome Measures: The primary outcome measure was confusion severity score as measured by the CAP after 14 days. The secondary outcome measures were (1) time to reach “nonconfused” CAP score; and (2) number of patients withdrawn from study due to predetermined, safety-related “escape” criteria. Results: There was no difference in the number of symptoms of PTCS, as measured by the CAP, between the AH and placebo-treated patients at day 14 of treatment (AH=2.56, placebo=2.7; Wilcoxon Mann-Whitney rank-sum test P=0.57). However, the mean difference in time to first “nonconfused” CAP score between groups approached significance (AH=7.7d, placebo=9.3d; Cox survival P=.053). No patients were withdrawn due to fulfillment of safety-related escape criteria. Conclusions: Although the natural course of symptom recovery from PTCS is favorable, these results provide tentative support to reports suggesting that AH safely hastens recovery from nonpenetrating TBI.

Long-Term Neuropsychological Outcome After Traumatic Brain Injury

To describe neuropsychological outcome 5 years after injury in persons with traumatic brain injury (TBI) who received inpatient medical rehabilitation. To determine the magnitude and pattern neuropsychological recovery from 1 year to 5 years after injury. Longitudinal cohort study with inclusion based on the availability of neuropsychological data at 1 year and 5 years after injury. National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems of Care. One hundred eighty-two persons with complicated mild to severe traumatic brain injury. Digits Forward and Backward, Logical Memory I and II, Token Test, Controlled Oral Word Association Test, Symbol Digit Modalities Test, Trail Making Test, Rey Auditory Verbal Learning Test, Visual Form Discrimination, Block Design, Wisconsin Card Sorting Test, and Grooved Pegboard. Significant variability in outcome was found 5 years after TBI, ranging from no measurable impairment to severe impairment on neuropsychological tests. Improvement from 1 year after injury to 5 years was also variable. Using the Reliable Change Index, 22.2% improved, 15.2% declined, and 62.6% were unchanged on test measures. Neuropsychological recovery after TBI is not uniform across individuals and neuropsychological domains. For a subset of persons with moderate to severe TBI, neuropsychological recovery may continue several years after injury with substantial recovery. For other persons, measurable impairment remains 5 years after injury. Improvement was most apparent on measures of cognitive speed, visuoconstruction, and verbal memory.